Factors Necessary For Erythropoiesis

Development and maturation of erythrocytes require variety of factors, which are classified into three categories:
1. General factors
2. Maturation factors
3. Factors necessary for hemoglobin formation.

GENERAL FACTORS OF ERYTHROPOIESIS

General factors necessary for erythropoiesis are:
i. Erythropoietin
ii. Thyroxine
iii. Hemopoietic growth factors
iv. Vitamins.

Erythropoietin

Erythropoiesis is stimulated by a kidney derived hormone called erythropoietin. It is also called hemopoietin or erythrocyte stimulating factor.Chemistry Erythropoietin is a glycoprotein with 165 amino acids.Source of secretion Major quantity of erythropoietin is secreted by peritubular capillaries of kidney. A small quantity is also secreted from liver and brain. Stimulant for secretion Hypoxia is the stimulant for the secretion of erythropoietin.

Actions of erythropoietin

Erythropoietin causes formation and release of new
RBCs into circulation. After secretion, it takes 4 to 5 days
to show the action.
Erythropoietin promotes the following processes:

• Production of proerythroblasts from CFU-E of the bone marrow.
• Development of proerythroblasts into matured
  RBCs through the several stages – early normoblast,
  intermediate normoblast, late normoblast
  and reticulocyte
  

• Release of matured erythrocytes into blood. Even some reticulocytes (immature erythrocytes) are
  released along with matured RBCs.
  

Blood level of erythropoietin increases in anemia.

Thyroxine

Being a general metabolic hormone, thyroxine accelerates the process of erythropoiesis at many levels.So, hyperthyroidism and polycythemia are common.

Hemopoietic Growth Factors

Hemopoietic growth factors or growth inducers are the interleukins and stem cell factor (steel factor). Generally these factors induce the proliferation of PHSCs. Interleukins (IL) are glycoproteins, which belong to the cytokines family.

Vitamins

Some vitamins are also necessary for the process of erythropoiesis. Deficiency of these vitamins cause anemia associated with other disorders. Vitamins necessary for erythropoiesis:

Vitamin B:

Its deficiency causes anemia and pellagra (disease characterized by skin lesions, diarrhea, weakness, nervousness and dementia).

Vitamin C:

Its deficiency causes anemia and scurvy (ancient disease characterized by impaired collagen synthesis resulting in rough skin, bleeding gum, loosening of teeth, poor wound healing, bone pain, lethargy and emotional changes).

Vitamin D:

Its deficiency causes anemia and
rickets

Vitamin E:

Its deficiency leads to anemia and malnutrition.

MATURATION FACTORS OF ERYTHROPOIESIS

Vitamin B12, intrinsic factor and folic acid are necessary
for the maturation of RBCs.

Vitamin B12 (Cyanocobalamin)

Vitamin B12 is the maturation factor necessary for
erythropoiesis.

Source of vitamin B 12

Vitamin B12 is called extrinsic factor since it is obtained mostly from diet. Its absorption from intestine requires the presence of intrinsic factor of Castle. Vitamin B12 is stored mostly in liver and in small quantity in muscle. When necessary, it is transported to the bone marrow to promote maturation of RBCs. It is also produced in the large intestine by the intestinal flora.

Action of cyanocobalmin

Vitamin B12 is essential for synthesis of DNA in RBCs.Its deficiency leads to failure in maturation of the cell and reduction in the cell division. Also, the cells are larger with fragile and weak cell membrane resulting in macrocytic anemia.Deficiency of vitamin B12 causes pernicious anemia. So, vitamin B12 is called antipernicious factor.

Intrinsic Factor of Castle

Intrinsic factor of castle is produced in gastric mucosa by the parietal cells of the gastric glands. It is essential for the absorption of vitamin B12 from intestine. In the absence of intrinsic factor, vitamin B12 is not absorbed from intestine. This leads to pernicious anemia. Deficiency of intrinsic factor occurs in:

• Severe gastritis
• Ulcer
• Gastrectomy.

Hematinic principle

Hematinic principle is the principle thought to be produced by the action of intrinsic factor on extrinsic factor. It is also called or antianemia principle. It is a maturation factor.

Folic Acid

Folic acid is also essential for maturation. It is required for the synthesis of DNA. In the absence of folic acid,the synthesis of DNA decreases causing failure of maturation. This leads to anemia in which the cells are larger and appear in megaloblastic (proerythroblastic) stage. And, anemia due to folic acid deficiency is called megaloblastic anemia.

FACTORS NECESSARY FOR HEMOGLOBIN FORMATION

Various materials are essential for the formation of hemoglobin
in the RBCs. Deficiency of these substances decreases the production of hemoglobin leading to anemia.Such factors are:

First class proteins and amino acids:

Proteins of high biological value are essential for the formation
of hemoglobin. Amino acids derived from these
proteins are required for the synthesis of protein
part of hemoglobin, i.e. the globin.

Iron:

Necessary for the formation of heme part of the hemoglobin.

Copper:

Necessary for the absorption of iron from the gastrointestinal tract. 

Cobalt and nickel:

These metals are essential for the utilization of iron during hemoglobin formation.

Vitamins:

Vitamin C, riboflavin, nicotinic acid and pyridoxine are also essential for the formation of hemoglobin. 

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also see " Factors Affecting Drug Metabolism
" detail notes on erythropoiesis "